Tackling typhoid fever burden in south Asia
Authors: Buddha Basnyat
Journal: The Lancet Global Health (2022)

South Asia is often thought to be a hub for enteric fever,1Basnyat B Qamar FN Rupali P Ahmed T Parry CM Enteric fever.BMJ. 2021; 372: n437Crossref PubMed Scopus (6) Google Scholar also called typhoid fever. Hence, the Article by Denise Garrett and colleagues in this issue of The Lancet Global Health,2Garrett DO Longley AT Aiemjoy K et al.Incidence of typhoid and paratyphoid fever in Bangladesh, Nepal, and Pakistan: results of the Surveillance for Enteric Fever in Asia Project.Lancet Glob Health. 2022; 10: e978-e988Summary Full Text Full Text PDF Scopus (2) Google Scholar which quantifies the burden of disease in these countries, is very welcome. Based on hard evidence of the kind that has been presented here, governments in this region can potentially make policy changes towards the control of enteric fever. However, at first glance the title might be misleading, as India, with its huge population and widespread typhoid fever, is not represented here. The authors, to their credit, explain this in the introduction of the Article, but the acronyms SEAP (Surveillance of Enteric Fever in Asia Project, which includes this present study) with its phase 1 and 2 components, and SEFI (Surveillance of Enteric Fever in India),3Journal of Infectious DiseasesBurden of Enteric Fever in India: a call to action.https://academic.oup.com/jid/issue/224/Supplement_5Date accessed: May 5, 2020Google Scholar which separately reports on the findings from India, might be confusing. Many doctors in south Asia perceive enteric fever to be on the decline, but this well-done burden study would seem to indicate that the problem is still very substantial. All the overall adjusted incidence rates for enteric fever, as clearly shown in the results by Garrett and colleagues from the various south Asian countries, are well over 100 per 100 000 person-years, which is the threshold used to define high-burden settings for enteric fever. In fact, another recently published study4Meiring JE Shakya M Khanam F et al.Burden of enteric fever at three urban sites in Africa and Asia: a multicentre population-based study.Lancet Glob Health. 2021; 9: e1688-e1696Summary Full Text Full Text PDF PubMed Scopus (7) Google Scholar in this journal reports an even higher burden in Nepal and Bangladesh than reported here by Garrett and colleagues. The reason for this discrepancy might be the methods used; the latter study4Meiring JE Shakya M Khanam F et al.Burden of enteric fever at three urban sites in Africa and Asia: a multicentre population-based study.Lancet Glob Health. 2021; 9: e1688-e1696Summary Full Text Full Text PDF PubMed Scopus (7) Google Scholar consistently used demographic census data, whereas Garrett and colleagues' study did not. The importance of WASH (water, sanitation, and hygiene) in controlling enteric fever is undisputed, but this (especially plumbing and sanitation improvements) is usually a long-term solution. In the meantime, vaccinations will be important. Based on WHO's recent recommendations5World Health OrganizationTyphoid vaccines: WHO position paper—March 2018.Wkly Epidemiol Rec. 2018; 13: 153-172Google Scholar and supportive findings from a randomised controlled trial6Shakya M Colin-Jones R Theiss-Nyland K et al.Phase 3 efficacy analysis of a typhoid conjugate vaccine trial in Nepal.N Engl J Med. 2019; 381: 2209-2218Crossref PubMed Scopus (84) Google Scholar (carried out in Lalitpur, Nepal), the Nepali Government, with the help of Gavi, the Vaccine Alliance, started a nationwide typhoid vaccination campaign from early April, 2022, following in the footsteps of Pakistan, which started an enteric fever vaccination drive after encountering widespread ceftriaxone resistance.7Qamar FN Yousafzai MT Khalid M et al.Outbreak investigation of ceftriaxone-resistant Salmonella enterica serotype Typhi and its risk factors among the general population in Hyderabad, Pakistan: a matched case-control study.Lancet Infect Dis. 2018; 18: 1368-1376Summary Full Text Full Text PDF PubMed Scopus (62) Google Scholar India and Bangladesh need to follow suit, given the high burden of enteric fever documented by this and other published studies such as SEFI3Journal of Infectious DiseasesBurden of Enteric Fever in India: a call to action.https://academic.oup.com/jid/issue/224/Supplement_5Date accessed: May 5, 2020Google Scholar and STRATAA (Strategic Typhoid Alliance across Africa and Asia)4Meiring JE Shakya M Khanam F et al.Burden of enteric fever at three urban sites in Africa and Asia: a multicentre population-based study.Lancet Glob Health. 2021; 9: e1688-e1696Summary Full Text Full Text PDF PubMed Scopus (7) Google Scholar from the region. There is another frightening aspect regarding enteric fever. Because of the easy availability of antibiotics without prescription in most pharmacies (despite laws mandating otherwise) in south Asia, treatment of suspected enteric fever with a variety of antibiotics is clearly contributing to antimicrobial resistance. Typhoid vaccine administration is a good example of how a single vaccine could potentially make a big difference in controlling antimicrobial resistance.8Birger R Antillón M Bilcke J et al.Estimating the effect of vaccination on antimicrobial-resistant typhoid fever in 73 countries supported by Gavi: a mathematical modelling study.Lancet Infect Dis. 2022; 22: 679-691Summary Full Text Full Text PDF PubMed Scopus (3) Google Scholar Effective vaccines are clearly key in fighting typhoid fever in settings where the burden, as illustrated by this Article, is daunting. But what is underemphasised is the need for proper treatment trials to establish the optimal antibiotic treatment for typhoid fever. These need to be carried out in places such as south Asia, especially against the background of rising antimicrobial resistance in typhoid treatment (the alarming situation of ceftriaxone resistance in enteric fever treatment in Pakistan7Qamar FN Yousafzai MT Khalid M et al.Outbreak investigation of ceftriaxone-resistant Salmonella enterica serotype Typhi and its risk factors among the general population in Hyderabad, Pakistan: a matched case-control study.Lancet Infect Dis. 2018; 18: 1368-1376Summary Full Text Full Text PDF PubMed Scopus (62) Google Scholar is a clear-cut example), the lack of new antibiotics in the pipeline, the unresolved treatment strategy of chronic Salmonella Typhi carriage, and the fact that there is no vaccine against paratyphoid fever. What is also underemphasised is that proper and effective treatment reduces carriage and is in and of itself a public health measure. In addition, these treatment trials need to be carried out, wherever possible, using a placebo to make the final results more robust and reliable.9Giri A Karkey A Dangol S et al.Trimethoprim-sulfamethoxazole versus azithromycin for the treatment of undifferentiated febrile illness in Nepal: a double-blind, randomized, placebo-controlled trial.Clin Infect Dis. 2021; 73: e1478-e1486Crossref PubMed Scopus (1) Google Scholar, 10Giri A Karkey A Dongol S et al.Azithromycin and cefixime combination versus azithromycin alone for the out-patient treatment of clinically suspected or confirmed uncomplicated typhoid fever in South Asia: a randomised controlled trial protocol.Wellcome Open Res. 2021; 6: 207Crossref PubMed Google Scholar Finally, typhoid diagnostics need to be improved, and the use of the unreliable Widal test stopped. In conclusion, the remarkable burden of typhoid fever as reported here by Garrett and colleagues must be duly appreciated so that control strategies, including use of the new typhoid conjugate vaccine, can be put in place. But, aside from WASH measures, what seems to be consistently ignored in tackling typhoid fever is the lack of emphasis on proper typhoid treatment trials with reliable, suitable diagnostics so that this disease can be effectively eliminated from areas of endemicity. I declare no competing interests. Incidence of typhoid and paratyphoid fever in Bangladesh, Nepal, and Pakistan: results of the Surveillance for Enteric Fever in Asia ProjectAcross diverse communities in three south Asian countries, adjusted incidence exceeded the threshold for "high burden" of enteric fever (100 per 100 000 person-years). Incidence was highest among children, although age patterns differed across sites. The substantial disease burden identified highlights the need for control measures, including improvements to water and sanitation infrastructure and the implementation of typhoid vaccines. Full-Text PDF Open Access